Dialysis is a treatment that removes the waste products and excess fluid which accumulate in the blood as a result of kidney failure. Peritoneal dialysis (PD) and hemodialysis are two forms of dialysis. Hemodialysis is a method of blood purification in which blood is continually removed from the body during a treatment session and passed through a dialyzer (artificial kidney) where metabolic waste and excess water are removed and pH and acid/base balances are normalized. The blood is concurrently returned to the patient's body. The dialyzer is a small disposable device consisting of a semi-permeable membrane. The membrane allows the wastes, electrolytes, and water to cross but restricts the passage of large molecular weight proteins and blood cells. Blood is pumped across one side of the membrane as dialysate is pumped in the opposite direction across the other side of the membrane. The dialysate is highly purified water with salts and electrolytes added. The machine is a control unit which acts to pump and control pressures, temperatures, and electrolyte concentrations of the blood and the dialysate. The average length of one hemodialysis treatment is 3-5 hours. Hemodialysis can be performed as single pass dialysis or sorbent-based dialysis.
Single-pass and sorbent dialysis systems both deliver dialysate to the dialyzer in prescribed amounts to cleanse the blood of impurities, correct the patient's body chemistry, and remove excess fluid. Sorbent dialysis differs from traditional single-pass dialysis in that sorbent systems use less water than single-pass machines and do not require special plumbing. Single-pass systems use approximately 120 liters of water during a typical 4-hour treatment. In single-pass dialysis, a water treatment system is required to continuously pump purified water into the system to be blended with the bicarbonate and acid bath to create the final dialysate. This requires special plumbing to connect the single-pass machine to both the water treatment system and to a drain into which the used dialysate and rejected source water are disposed.
By utilizing sorbent technology, a dialysis system can provide dialysate for 3- to 5-hour dialysis treatments using 6-12 liters of potable tap water. The sorbent cartridge purifies the initial dialysate (formed from the tap water) and continuously recirculates and regenerates the dialysate throughout the treatment. Sorbent dialysis does not require a continuous water source, a separate water purification machine or a floor drain because it continuously regenerates a small volume of dialysate and thus incorporates a water treatment system within the machine. In addition, sorbent systems can use a lower amperage electrical source because they recycle the same small volume of dialysate throughout the dialysis procedure. The heavy duty dialysate pumps and heaters used for large volumes of dialysate in single pass dialysis are not needed. Sorbent dialysis provides a high degree of portability compared to single pass dialysis.
Sorbent dialysis uses a sorbent cartridge, which acts both as a water purifier and as a means to regenerate used (spent) dialysate into fresh dialysate. During a sorbent dialysis treatment, urea is decomposed within the sorbent cartridge, uremic wastes are removed, and dialysate pH and electrolyte balances are maintained. A sorbent cartridge including zirconium phosphate (ZrP) and hydrous zirconium oxide (HZO) ion-exchange materials has been historically used for the REDY (REgenerative DialYsis) system. The REDY sorbent cartridge has several layers through which used dialysate passes. The scheme of the REDY cartridge is shown in FIG. 1. The sorbent cartridge is shown with the inlet and the outlet identified as numeral 11 and numeral 13, respectively. FIG. 2 shows various functions of each layer in a REDY cartridge. The principle of the REDY cartridge is based on the hydrolysis of urea to ammonium carbonate by the enzymatic reaction with urease. FIGS. 1-2 show alumina supported urease. The following equation shows a reaction for urea conversion to ammonia in the presence of urease:
The ammonia and ammonium ions are then removed by the zirconium phosphate in exchange for the hydrogen ions and Na+ ions, which are counter-ions in the cation exchanger. Zirconium phosphate also serves as cation exchanger to remove Ca+, Mg+, K+, and other cations in dialysate. The carbonate from the urea hydrolysis then combines with the hydrogen ions in zirconium phosphate to form bicarbonate, which is delivered to the uremic patient as a base to correct for acidosis. Zirconium phosphate can be represented as inorganic cation exchange material with the molecular structure as shown below:
As shown, the material contains both H+ and Na+ as counter-ions, which are responsible for ion exchange. The relative content of these ions can be controlled by the pH to which acid ZrP (or H+ZrP) is titrated with NaOH. The composition of the resultant product of titration, Nax+H2-x+ZrP (or abbreviated as “NaHZrP” herein), may vary during ion exchange processes in dialyate. The hydrous zirconium oxide (HZO) containing acetate (HZO.Ac) as a counter ion serves as an anion exchanger to remove phosphate. The material also prevents leaching of phosphate from NaHZrP and removes anions (e.g., fluoride) in water that may cause harm to a patient during dialysis. The acetate released during ion exchange is also a base to correct for acidosis by acetate metabolism. The compositional formula of hydrous zirconium oxide (HZO) can be ZrO2.nH2O (i.e. zirconium oxide hydrate) or ZrO2.nOH . . . H+An− in the anion form wherein An is an anion attached to HZO, such as acetate (“Ac”), chloride, etc. Without the anion, it can be considered as partially oxalated zirconium hydroxide with various degrees of O2−, OH− and H2O bonded to Zr, i.e., Zr(OH)xOy(H2O)z. The granular activated carbon in the cartridge is used in the REDY cartridge for the removal of creatinine, uric acid, and nitrogenous metabolic waste of the patient as well as chlorine and chloramine from water. Thus the REDY regenerative dialysis system is efficient to provide both safety and simplicity of water treatment and hence convenience for hemodialysis. The efficacy and safety record of the system has been well established.
Potable tap water in 6 liter volumes and prescribed amounts of sodium chloride, sodium bicarbonate, and dextrose have been used to create the initial (precursor) dialysate solution for sorbent dialysis. The preparation of the precursor dialysate solution can involve dissolving and mixing the electrolytes and sugar with tap water in large jugs, for example, in a 6-liter jug. The measuring and mixing involved can be prone to error. Before passing through the dialyzer during prime, the precursor dialysate solution is passed through the sorbent cartridge for purification. As it flows through the sorbent cartridge, impurities such as bacteria, pyrogens, endotoxins, metals, and organic solutes are removed from the precursor dialysate solution. The purified dialysate is stored in a dialysate reservoir until it is circulated to the dialyzer. Once it leaves the dialyzer, the used (spent) dialysate, which includes a patient's ultrafiltrate fluid, passes through the sorbent cartridge, for conversion into regenerated dialysate, also known as cartridge effluent. As indicated, zirconium phosphate present in the sorbent cartridge also serves as a cation exchanger to remove Ca+, Mg+, K+, and other cations in dialysate. An infusate system adds calcium, magnesium, and potassium electrolytes to the regenerated dialysate, thus allowing a balance of electrolyte level in the patient's blood (Ca, Mg, K) to be maintained as well as providing safety for dialysis treatment with regard to water quality. The regenerated dialysate then flows back into a dialysate reservoir, ready to be sent to the dialyzer. In a conventional “6-liter” system, the waste dialysate that must be disposed of after a dialysis treatment can significantly exceed six liters in volume.
A dialysis system that uses less volume of dialysate, eliminates bicarbonate requirements in the precursor dialysate (priming) solution to reduce ingredient amounts, preparation steps and formulation complexity, uses smaller scale components for increased portability and convenience, produces less waste, and/or that can be easily and cost-effectively resupplied, while maintaining purity standards, would be desirable.